DISEASE/DRUG OF INTEREST: Hepatitis B / Hepatitis B vaccine
MOTIVATION AND BACKGROUND: Hepatitis B is an infectious disease that has affected two billion people worldwide. More than 50% of liver cancers worldwide are attributed to HBV infection [2]. The Hepatitis B virus (HBV) causes Hepatitis B by injecting its DNA into livers cells. Hepatitis B inflames the liver, so that it will not process nutrients or filter toxins from blood. Some symptoms of Hepatitis B are fever, fatigue, nausea, joint pain, dark urine, and jaundice. If left untreated, Hepatitis B can lead to cirrhosis or liver cancer. There are treatments for Hepatitis B, but the most effect way to prevent the illness is to take the Hepatitis B vaccine to fight off the infection once exposed. There are two types of Hepatitis B - acute and chronic. Acute Hepatitis may only last for a few weeks to a few months. Usually when children come in contact with the infection they do not have symptoms, but adults have symptoms within three months of exposure. If Hepatitis B is still detectable after six months that means the person has chronic Hepatitis B. In other words, the virus is unable to be removed and the person will be a Hepatitis B carrier. Chronic Hepatitis B can last a lifetime, but may not show symptoms until later on in life. Even though there may not be symptoms, Hepatitis B can still inflame the liver and will most likely take decades for symptoms to develop that are similar to acute Hepatitis B. Hepatitis B is usually spread when infected blood, semen or other bodily fluids infiltrate someone else. Therefore, being sexually active, sharing needles or through any related action may cause someone to become infected by the virus. Those who have many sexual partners or even someone who lives with a Hepatitis B carrier are at risk of being infected by the virus. Children may even inherit the infection through childbirth from their mother. Once the virus infects the liver it is able to travel throughout the body by blood. Those who are suspected of being infected should be diagnosed by a blood test.
Fig 1: Geographic distribution of chronic hepatitis B virus (HBV) infection, 2005* [1].
TARGET INFORMATION: Hepatitis B is diagnosed via a blood test that detects the presence of Hepatitis B surface antigen (HBsAG) within the blood stream. The presence of HBsAG is the first sign that one has contracted Hepatitis B. If someone was able to treat Hepatitis B then the presence of HBsAG will no longer be detectable. Hepatitis B is a virus that attacks liver cells; by binding to hepatocytes the virus is able to insert and express its genetic code. The receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver [2]. The NTCP allows the virus to bind and enter the cell by endocytosis. The DNA of the virus is released into the cytoplasm and travels to the nucleus to be translated, replicated, and expressed. Millions of cells will multiply through mitosis, cell replication, including the virus now embedded with the liver cells original DNA. Hepatitis B virus will continue to multiply and eventually harden the liver until it is unable to function. Once the immune system recognizes that HBV has infiltrated the body there are cells that mature to fight against the virus. The immune system alone will fight off the infection, but sometimes the immune system will not completely prevent or cure the disease. Fig 2: Structure and genomic oragization of hepatitis B virus [3]. DRUG INFORMATION: The best way to prevent Hepatitis B virus is getting the Hepatitis B vaccine. Vaccines usually contain a weakened virus or bacterium that causes a certain disease. In order to make Hepatitis B vaccine, certain Hepatitis B genetic material must be inserted into yeast cells to produce Hepatitis B surface antigen (HBsAG). The Hepatitis B vaccine contains HBsAG, so that HBsAG will bind to B lymphocytes and will react as if the real infection has been injected into the body to produce memory cells and plasma cells. The vaccine produces plasma cells that secrete Hepatitis B surface antigen to surround and nullify the virus. The view that Hepatitis B exerts its damaging effect on hepatocytes by direct cytopathic changes is inconsistent with the persistence of large quantities of surface antigen in liver cells of many apparently healthy persons who are carriers [3]. Although, after a period of time the antibodies will disappear if the virus has not attacked yet, the memory cells altered by the vaccination will still stay alive to produce antibodies again just in case one is injected with the Hepatitis B virus. This vaccine is administered by shot usually by 3-4 shots over six months. The first shot is administered at any time, the second shot is later receive a month after, and the last shot is received six months after the first dose. Side effects of the vaccine include numbing of the injection area and a fever of less than 99.9 degrees Fahrenheit, but in most cases, those side effects are very rare [1]. In fact, a fever from the vaccine is about 1-6 percent and was around the same for the placebo group. Fig 3: HBsAg consists of three related proteins: the large, middle and small surface antigens, all encoded by the same reading frame. The large antigen consists of preS1, preS2, and HBsAg. The binding site for liver cells is located in preS1. HBsAg is a hydrophobic protein arranged such that the central part (aa 100-160) is located on the surface of the viral particle and forms a major, immunodominant, hydrophilic region [4]. The HBsAg is what makes up the vaccine. Fig 4: The basic process of how the HB vaccine is produced [5].
REFERENCES: 1. Mast, E. E.; Margolis, H. S.; Fiore, A. E.; Brink, E. W.; Goldstein, S. T.; Wang, S. A.; Moyer, L. A.; Bell, B. P.; Alter, M. J.; (ACIP), A. C. o. I. P., A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep2005,54 (RR-16), 1-31.
2. Yan, H.; Zhong, G.; Xu, G.; He, W.; Jing, Z.; Gao, Z.; Huang, Y.; Qi, Y.; Peng, B.; Wang, H.; Fu, L.; Song, M.; Chen, P.; Gao, W.; Ren, B.; Sun, Y.; Cai, T.; Feng, X.; Sui, J.; Li, W., Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife2012,1, e00049.
3. Zuckerman, A. J., Hepatitis Viruses. In Medical Microbiology, Baron, S., Ed. University of Texas Medical Branch at Galveston The University of Texas Medical Branch at Galveston: Galveston (TX), 1996.
Hepatitis B / Hepatitis B vaccine
MOTIVATION AND BACKGROUND:
Hepatitis B is an infectious disease that has affected two billion people worldwide. More than 50% of liver cancers worldwide are attributed to HBV infection [2]. The Hepatitis B virus (HBV) causes Hepatitis B by injecting its DNA into livers cells. Hepatitis B inflames the liver, so that it will not process nutrients or filter toxins from blood. Some symptoms of Hepatitis B are fever, fatigue, nausea, joint pain, dark urine, and jaundice. If left untreated, Hepatitis B can lead to cirrhosis or liver cancer. There are treatments for Hepatitis B, but the most effect way to prevent the illness is to take the Hepatitis B vaccine to fight off the infection once exposed.
There are two types of Hepatitis B - acute and chronic. Acute Hepatitis may only last for a few weeks to a few months. Usually when children come in contact with the infection they do not have symptoms, but adults have symptoms within three months of exposure. If Hepatitis B is still detectable after six months that means the person has chronic Hepatitis B. In other words, the virus is unable to be removed and the person will be a Hepatitis B carrier. Chronic Hepatitis B can last a lifetime, but may not show symptoms until later on in life. Even though there may not be symptoms, Hepatitis B can still inflame the liver and will most likely take decades for symptoms to develop that are similar to acute Hepatitis B. Hepatitis B is usually spread when infected blood, semen or other bodily fluids infiltrate someone else. Therefore, being sexually active, sharing needles or through any related action may cause someone to become infected by the virus. Those who have many sexual partners or even someone who lives with a Hepatitis B carrier are at risk of being infected by the virus. Children may even inherit the infection through childbirth from their mother. Once the virus infects the liver it is able to travel throughout the body by blood. Those who are suspected of being infected should be diagnosed by a blood test.
Fig 1: Geographic distribution of chronic hepatitis B virus (HBV) infection, 2005* [1].
TARGET INFORMATION:
Hepatitis B is diagnosed via a blood test that detects the presence of Hepatitis B surface antigen (HBsAG) within the blood stream. The presence of HBsAG is the first sign that one has contracted Hepatitis B. If someone was able to treat Hepatitis B then the presence of HBsAG will no longer be detectable. Hepatitis B is a virus that attacks liver cells; by binding to hepatocytes the virus is able to insert and express its genetic code. The receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver [2]. The NTCP allows the virus to bind and enter the cell by endocytosis. The DNA of the virus is released into the cytoplasm and travels to the nucleus to be translated, replicated, and expressed. Millions of cells will multiply through mitosis, cell replication, including the virus now embedded with the liver cells original DNA. Hepatitis B virus will continue to multiply and eventually harden the liver until it is unable to function. Once the immune system recognizes that HBV has infiltrated the body there are cells that mature to fight against the virus. The immune system alone will fight off the infection, but sometimes the immune system will not completely prevent or cure the disease.
Fig 2: Structure and genomic oragization of hepatitis B virus [3].
DRUG INFORMATION:
The best way to prevent Hepatitis B virus is getting the Hepatitis B vaccine. Vaccines usually contain a weakened virus or bacterium that causes a certain disease. In order to make Hepatitis B vaccine, certain Hepatitis B genetic material must be inserted into yeast cells to produce Hepatitis B surface antigen (HBsAG). The Hepatitis B vaccine contains HBsAG, so that HBsAG will bind to B lymphocytes and will react as if the real infection has been injected into the body to produce memory cells and plasma cells. The vaccine produces plasma cells that secrete Hepatitis B surface antigen to surround and nullify the virus. The view that Hepatitis B exerts its damaging effect on hepatocytes by direct cytopathic changes is inconsistent with the persistence of large quantities of surface antigen in liver cells of many apparently healthy persons who are carriers [3]. Although, after a period of time the antibodies will disappear if the virus has not attacked yet, the memory cells altered by the vaccination will still stay alive to produce antibodies again just in case one is injected with the Hepatitis B virus. This vaccine is administered by shot usually by 3-4 shots over six months. The first shot is administered at any time, the second shot is later receive a month after, and the last shot is received six months after the first dose. Side effects of the vaccine include numbing of the injection area and a fever of less than 99.9 degrees Fahrenheit, but in most cases, those side effects are very rare [1]. In fact, a fever from the vaccine is about 1-6 percent and was around the same for the placebo group.
Fig 3: HBsAg consists of three related proteins: the large, middle and small surface antigens, all encoded by the same reading frame. The large antigen consists of preS1, preS2, and HBsAg. The binding site for liver cells is located in preS1. HBsAg is a hydrophobic protein arranged such that the central part (aa 100-160) is located on the surface of the viral particle and forms a major, immunodominant, hydrophilic region [4]. The HBsAg is what makes up the vaccine.
Fig 4: The basic process of how the HB vaccine is produced [5].
REFERENCES:
1. Mast, E. E.; Margolis, H. S.; Fiore, A. E.; Brink, E. W.; Goldstein, S. T.; Wang, S. A.; Moyer, L. A.; Bell, B. P.; Alter, M. J.; (ACIP), A. C. o. I. P., A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 2005, 54 (RR-16), 1-31.
2. Yan, H.; Zhong, G.; Xu, G.; He, W.; Jing, Z.; Gao, Z.; Huang, Y.; Qi, Y.; Peng, B.; Wang, H.; Fu, L.; Song, M.; Chen, P.; Gao, W.; Ren, B.; Sun, Y.; Cai, T.; Feng, X.; Sui, J.; Li, W., Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 2012, 1, e00049.
3. Zuckerman, A. J., Hepatitis Viruses. In Medical Microbiology, Baron, S., Ed. University of Texas Medical Branch at Galveston
The University of Texas Medical Branch at Galveston: Galveston (TX), 1996.
4. New FIRE System. Vaccines. Subunit Vaccines. http://nfs.unipv.it/nfs/minf/dispense/immunology/lectures/files/vaccines.html#section5
5. Health and Medicine. Production of Recombivax HB. https://www.ied.edu.hk/biotech/eng/classrm/class_health5.html